tbuckley/cabot-search huggingface dataset:
Effect of an oncology care management program on unplanned hospital admissions in a commercially insured population.
Authors: Wendy L. French, Callie B Beagley, Erica Stevens, Elizabeth R Parker, Angelica I Norrell, Lisa A Doelger, William A. Flood, Lisa M Latts
Journal: Journal of Clinical Oncology (2023)

1547 Background: Despite advances in cancer outcomes, costs of cancer care continue to rise. Acute care utilization contributes significantly to these costs. The Cancer Support Program’s (CSP) care management services focus on providing education on symptom management, palliative care and advance care planning, addressing psychosocial needs and closing gaps in care in members with cancer who are at high risk for unplanned hospital admissions (UHA). Methods: Beginning 1/1/22, commercially insured members with an active cancer diagnosis were clinically stratified as high or low risk for UHA. All high-risk members were invited to participate in the CSP program. Individuals who agreed to participate received individualized telephonic care management support. Medical claims from 1/1/22 through 9/30/22 were evaluated, and rates of UHA were compared between participants and non-participants within the identified high-risk population for an average period of 4 months after identification (the period equivalent to the average enrollment period of participants). Results: The study population included 3,113 members who stratified as high risk. Of those, 36% were enrolled in the program. Reasons for non-enrollment include inability to reach (72%), member refused (27%) and bad contact information (1%). There were no statistically significant differences between the two groups’ demographic composition except for age (the enrolled group had slightly more in the 51-64 age group [63% vs. 59%; p &lt; 0.001] and slightly fewer in the &gt; 65 age group (9% vs. 15%; p &lt; 0.001]). There were 358 UHA in the participating group and 737 UHA in the non-participating group. When normalized, there were 1,179 UHA per thousand members per year (PTMPY), 99% CI [1,171 UHA, 1,184 UHA] (bootstrap) in the participating group and 1,526 UHA PTMPY, 99% CI [1,523 UHA, 1,535 UHA] (bootstrap) in the non-participating group. Conclusions: Early results show lower UHA rates for members who participated in the care management program, suggesting the program is effective in reducing acute care utilization within the high-risk population. Limitations of this study include potential enrollment bias, changes in risk status from clinical or social factors, and the potential for human error or inconsistency in the risk stratification process. Further study is underway to validate these results.
Effect of suppressing the p38 pathway through upregulation of Wip1 on Her2 early dissemination of breast cancer.
Authors: Nan Wang, Peiqing Sun, Hong Liu
Journal: Journal of Clinical Oncology (2023)

e13029 Background: Metastasis is the leading cause of cancer-related deaths. While mechanisms for metastasis were extensively studied in cancer cells from patients with detectable tumors, pathways underlying metastatic dissemination from early lesions are poorly understood. Her2 promotes breast cancer early dissemination by suppressing p38, but how it downregulates p38 is unclear. In this study, we investigated the mechanism underlying suppression of p38 by Her2 in breast cancer early dissemination using cell models of early lesions of breast cancer. Methods: We studied the role of Wip1 in disseminating phenotypes in cell line models of breast cancer early lesions. These disseminating phenotypes include cell motility measured in transwell assays, cell invasion measured by percentage of organoids with outwards in organoid-forming medium, and epithelial-to-mesenchymal transition (EMT) measured by E-cadherin and Vimentin levels in Western blotting analysis, percentage of organoids with High E-cadherin junctions and nuclear translocation and activation of β-catenin in immunofluorescence (IF) staining assays. Results: We demonstrate that high levels of Wip1, a p38 phosphatase, correlated with Her2+ status, and reduced phosphorylation of p38 and its downstream effectors MK2 and Hsp27 in tissue samples and cell models of breast cancer early lesions. We found that Wip1 promoted migration, invasion and EMT, while Wip1 knockdown abrogated the ability of Her2 to induce these disseminating phenotypes, in cell line models of early lesion of breast cancer. In contrast to the wild type Wip1, the catalytically inactive mutants of Wip1 failed to induce the disseminating phenotypes. Thus, Wip1 induction is both sufficient, and necessary for Her2, to promote migration, invasion and EMT in breast cancer early lesion cells. In an attempt to identify the Wip1 downstream effectors involved in disseminating phenotypes, we found that ectopic expression of the constitutively active mutants of p38γ and δ, but not that of p38α and β, reversed the ability of Wip1 to suppress MK2 and Hsp27 phosphorylation and to induce migration, invasion and EMT. It suggests that Wip1 promotes the early dissemination by suppressing p38γ and δ. We investigate the mechanism by which Her2 induces Wip1 expression. Ectopic expression of Her2 did not alter the level of Wip1 mRNA or the Wip1 protein stability, suggesting that Her2 may promote Wip1 expression by regulating its translation. Moreover, inhibitors of Her2, Wip1 and Skp2 can each reduce the disseminating phenotypes in cells models of breast cancer early lesions ectopically expressing Her2, Wip1 or Skp2. Conclusions: Our findings identify the Her2-Wip1-p38-Mk2-Hsp27 cascade as a novel mechanism mediating breast cancer early dissemination and provide a basis for new therapies targeting early metastatic dissemination in Her2+ breast cancer using inhibitors for Her2, Wip1 or Skp2.
Tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery in locally advanced hypopharyngeal squamous cell carcinoma: A single-arm, phase II trial.
Authors: Lin Gui, Shaoyan Liu, Xiaolei Wang, Ye Zhang, Xiaohui He
Journal: Journal of Clinical Oncology (2023)

6087 Background: Induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) is the standard of care for locally advanced hypopharyngeal squamous cell carcinoma (LA HPSCC). We aimed to assess whether add immunotherapy to ICT further improving patient outcomes. Methods: In this phase II, single-arm study, eligible pts aged 18-70 yrs diagnosed with stage III-IVB (AJCC 8 th ) HPSCC received induction therapy with tislelizumab (200 mg), cisplatin (75 mg/m 2 ) and nab-paclitaxel (260 mg/m 2 ) Q3W for 3 cycles. After assessment by multidisciplinary team, pts received surgery or CRT. The primary endpoint was objective response rate (ORR). Secondary endpoints include major pathologic response (MPR) in surgery group, disease control rate (DCR), 2-yr PFS rate in CRT group and 2-yr DFS rate. Results: 29 pts were enrolled (median age, 61 y; 97% male; stage III/IVA/IVB, 7%/90%/3%) from May to Nov 2022. Median follow-up was 7.3 months, no disease progression occurred in all patients. For all pts, the post-induction ORR and DCR were 82% and 100%. In surgery group (n = 10), all pts achieved R0 resection, and 5 (50%) pts reached pathological complete response (pCR). A patient with stable disease underwent a total laryngectomy achieved pCR by postoperative pathologic evaluation. Grade 3 and 4 treatment-related adverse event (TRAE) reached 82.8%, and mainly come from chemotherapy-related neutropenia. There was no TRAE leading to treatment discontinuation. Conclusions: These early data suggested that tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery was safe and had the potential to provide clinical benefits for patients in LA HPSCC. The inconsistency between radiographic and pathological evaluation needs further exploration. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200060094 .
Efficacy of abemaciclib versus tucidinostat after progression on palbociclib in patients with HR+/HER2− MBC: A multicenter retrospective cohort study.
Authors: Yang Yuan, Shaohua Zhang, Tao Wang, Biyun Wang, Shusen Wang, Jing Shi, Tao Sun, Yongmei Yin, Quchang Ouyang, Jianbin Li, Yi Wen, Lijun Zhang, Zefei Jiang
Journal: Journal of Clinical Oncology (2023)

e13056 Background: For patients with hormone receptor-positive HER2-negeative metastatic breast cancer (HR+HER2-MBC), switching to another cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) or target drug with different mechanism are reasonable treatment strategies post-CDK4/6i. However, no clinical data has been reported on which of the two strategies is more effective. We performed a retrospective cohort study to evaluate the efficacy of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib. Methods: We identified patients with HR+/HER2- MBC who received abemaciclib-based therapy or tucidinostat-based therapy after progression on palbociclib from seven research centers in China. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate (CBR), PFS in patients with PIK3CA-mutant and PIK3CA wild-type, and safety. Results: Between Apr 1 st 2020 and September 30 th 2022, a total of 149 patients were included, of whom 73 patients received abemaciclib plus endocrine therapy(ET), and 76 patients received tucidinostat plus ET. The majority of patients had visceral disease (124/149, 83.2%) and ≥3 metastatic sites (76/149, 51.0%) at baseline, one third of patients (48/149, 32.2%) had previously been treated ≥3 lines of endocrine therapy in MBC setting. More patients received sequential therapy after palbociclib in abemaciclib group(49.3%) than that in tucidinostat group(30.3%). There were no statistically significant differences in other baseline characteristics between the two groups. Clinical benefit rate (CBR) was 38.4% (28/73) in abemaciclib group and 17.1% (13/76) in ET plus tucidinostat group (p=0.0037). There was significant difference in PFS between abemaciclib group and tucidinostat group in both the whole population (5.0 months vs. 2.0 months; HR 0.44; 95%CI 0.31-0.64; P＜0.001) and propensity score matched population. PIK3CA mutations occurred in 44.20% of patients who had undergone multigene sequencing. PIK3CA-mutant showed a negative effect on PFS of abemaciclib-based therapy. The most common any grade and grade 3-4 adverse events was neutropenia in either group. Common non-hematological toxicity occurred in abemaciclib group was diarrhea, and were increased AST, nausea, vomiting in tucidinostat group. Conclusions: Abemaciclib-based therapy improved clinical benefit rate and prolonged PFS compared with tucidinostat-based therapy, providing a superior treatment option in patients progressed on palbociclib.
Measuring time toxicity of systemic therapies for advanced esophageal and gastric cancers.
Authors: Neha Agrawal, Rajat Thawani, Emerson Yu-sheng Chen
Journal: Journal of Clinical Oncology (2023)

e13660 Background: Immunotherapy checkpoint inhibitors have demonstrated clinical benefit in esophago-gastric cancers. Little is known regarding time spent on treatment and adverse events that patients experienced to receive their care, or time toxicity, with regards to advances in immunotherapy. Methods: Fifteen phase 3 trials of anti-PD1 and anti-PDL1 inhibitors used for esophageal and gastric cancers were selected from clinicaltrials.gov if they were published by February 2021. The published methods and protocol were reviewed to estimate the number of ‘hospital days’ based on required procedures associated with screening and treatment related care and proportion of serious and severe adverse events that served as a surrogate for time toxicity. Once hospital days were estimated for all randomized groups, they were analyzed according to immunotherapy arms, which included chemo-immunotherapy and immunotherapy-only arms, and non-immunotherapy arms, which included chemotherapy only and observation arms. Results: From the 15 trials included, there were 32 randomized groups, as 2 trials had 3 randomized groups. Six trials eventually led to FDA approval. Six were for immune checkpoint inhibitors in first line setting, and 8 were in subsequent line setting, and 1 were in adjuvant or maintenance trials. Only pembrolizumab, nivolumab, and avelumab were represented. The median estimated hospital days was 38 days (range 7-52), or 1.3 months, over one year. There was no difference comparing immunotherapy vs. immunotherapy-free arms (p = 0.5), but there was difference comparing chemotherapy vs. chemotherapy-free arms (p &lt; .05). The median survival in the group of patients who received combination chemo-immunotherapy was 13.9 months, with time toxicity of 1.4 months. The survival and time toxicity of the chemotherapy, immunotherapy and placebo arms were 9.1 and 1.3 months, 10 and 0.9 months, and 7.5 and 0.3 months, respectively. Conclusions: While there is substantial number of days committed to cancer therapies among patients with esophageal or gastric cancer, we noticed a trend of more time toxicity in patients who received chemo-immunotherapy, vs patients who received immunotherapy alone. Given the modest improvement in survival gleaned from these trials, the magnitude of survival benefit should be weighed against the time toxicity incurred in patients.
Optimization of a deep convolution neural network (DCNN) for osteosarcoma necrosis quantification and outcome prediction.
Authors: Michael Occidental, Nicolas Coudray, Aristotelis Tsirigos, George Jour
Journal: Journal of Clinical Oncology (2023)

e13541 Background: Deep convolutional neural network is a form of artificial intelligence that gained traction recently in diagnostic and prognostic applications such as automated tissue segmentation and outcome and response to immunotherapy prediction. Herein, we optimize DCNN to accurately segment and quantify necrosis in osteosarcoma (OSA) archival slides. We also correlate the AI driven necrosis ratios with those derived from experienced sarcoma pathologists (gold standard) and show their value in predicting patient’s outcomes. Methods: A total of 44 patients with bone resections for primary high-grade osteosarcomas post neoadjuvant treatment with conventional chemotherapy were included (Male n= 26, female n=19), median age = 16.4 years. 103 slides from 21 patients were originally manually segmented and used for initial training using 3-fold cross-validation split per patient and per slide. Here, an additional 119 slides from 23 patients (total of 222 slides) were added in the retraining for automated segmentation and to update the necrosis ratio calculation, and the correlation with pathologist calculated necrosis ratio (R spearman correlation). Based on this ratio, we performed a prediction of Overall survival using the Log rank test. Results: The segmentation classifier identified viable tumor, necrosis, normal tissue and artefacts within slides with an area under the curve ranging from 0.91 to 0.96. AI necrosis ratio showed a good correlation with pathologist driven ration (R=0.74 per slide, R=0.69 per patient). Some outliers with highest discrepancy for necrosis ratio included surface high grade periosteal osteosarcomas (known for cartilaginous differentiation that is not part of the original training of the algorithm). Patients with an AI necrosis ratio of ≥ 70% had a better Overall survival at 36 months (p=0.01). Conclusions: Our results show the potential of integration of DCNN for automated segmentation and necrosis quantification of central high OSA resection enhancing efficiency in interpreting these complex surgical specimens. The data also suggests a possible prognostic application of the AI derived necrosis ratio. Further validation of the DCNN performance on an independent cohort is underway.
The PLATON Network: An interactive platform for precision oncology.
Authors: Salah-Eddin Al-Batran, Thorsten Oliver Goetze, Anna Lena Saborowski, Nihat Bugra Agaoglu, Sebastian Broeckling, Clara Dreyling, Sylvie Lorenzen, Dominik Paul Modest, Markus K Schuler, Benedikt Westphalen, Peter Wild, Bianca Zäpf, Arndt Vogel
Journal: Journal of Clinical Oncology (2023)

TPS1613 Background: To increase the access of patients to precision oncology and personalized medicine, we need not only to undertake molecular profiling but rather we need to interlink patients, physicians and researchers using modern technological opportunities, increasing the likelihood of providing new therapies to patients with suitable targets. The PLATON Network (NCT05489250, IKF-T008) addresses these important issues. Methods: The PLATON Network (PLATON) is an interactive structure aiming at improving personalized medicine for all tumor entities (starting with upper GI tumors). The goal of the PLATON Network is to provide a platform for connecting medical practitioners, researchers and patients to personalized cancer treatments. The platform combines comprehensive molecular profiling, data on active clinical trials, remote data access with networking solutions, implemented substudies and associated educational and discussion forums. The main elements of PLATON are: a Platform-study design, an interactive Cloud-based WebApp, Networking, a Molecular Pathology Case Discussion Board, an educational forum, and a BioDataBank. The network will be composed of a global network of cancer centers and cancer specialists who can submit genomic data of their patients to PLATON. The WebApp allows members and associated scientists to view each other's current patients' clinical and molecular data and get into contact with the treating physicians or identify patients for ongoing biomarker-driven clinical trials using advanced algorithms. The PLATON Network also offers molecular testing via Foundation CDx and CDx Liquid for standardized NGS testing and functions as an umbrella for substudies within the platform design. PLATON enrolls patients during first line treatment and collects information on routine clinical data (baseline data, medical history, histopathology reports, treatment decisions, etc.). During follow up, all anti tumor therapy lines, tumor response and survival data are recorded. Importantly, quality of life data is captured monthly under therapy (with EORTC QLQ-30,-BIL21, -HCC18, -PAN26, -STO22 and EQ-5D-5L) and at further follow up (with EQ-5D-5L). So far, 110 cancer centers have joined the PLATON network. Over 200 patients with upper GI tumors received comprehensive molecular profiling and 162 cases were reviewed and discussed in the Molecular Pathology Case Discussion Board. Five sub-projects/-studies have been initiated under the umbrella of PLATON. The educational forum is in the planning stage. PLATON is conducted by the Institute of Clinical Cancer Research (IKF) in Frankfurt with the supervision of an independent scientific steering committee.
Implementation of the novel use of an objective scoring rubric to reduce utilization of inpatient non-formulary chemotherapy.
Authors: Aarti Sonia Bhardwaj, Priya Jain, Robert Thomas, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2023)

e13535 Background: The cost of cancer care is an enormous healthcare burden. Most inpatient chemotherapy (IC) is not reimbursed because of diagnosis-related group codes. We implemented the use of a novel objective scoring rubric to guide and automate IC stewardship at an academic cancer center to decrease the inappropriate use of costly inpatient therapies in patients especially at the end of life. Methods: We created a scoring rubric based on treatment and regimen specific criteria. IC that is on formulary and standard of care is automatically approved. IC that is non-formulary requires evaluation using the developed criteria. Treatment factors include: type and phase of trial, and FDA and NCCN approvals. Patient factors include: performance status, line and goal of therapy. Clinicians must complete the criteria via a form in RedCap which then automatically calculates a score which is then reviewed by 2 disease specific physicians and a clinical pharmacist for accuracy. If the threshold score is met, IC is approved and if it is not met, IC is not approved for administration. Our primary outcome is cost savings and clinical outcomes. Results: Pre-implementation the cost of IV NF chemotherapy from 3/2021-10/2021 was $744,105 and post –implementation from 3/2022-10/2022 was $549,363 which is a 26% ($194,741) reduction in cost. 98 cases were reviewed over this time period. 82 (84%) cases were approved and 16 (16%) were disproved. The total cost of approved cases was $482,694 and the cost savings of disproved cases was $68,121 (14%). 51 were Solid Tumor (ST) requests and 47 were for Heme Malignancy (HM) requests. Clinical outcomes of the approved cases are illustrated. 16% of cases were submissions for immunotherapy (nivolumab, pembrolizumab) and 81% of those patients died. Conclusions: 84% of the time our cancer physicians chose the administration of IC that aligned with objective criteria which is reassuring and serves to validate the use of this tool. Alternatively, this tool prevented inappropriate administration of chemotherapy 16% of the time. Our pilot indicates that there is a role for an objective tool for automated IC stewardship.[Table: see text]